2-Decarboxy-2-aminomethyl-6-hydroxy-PGE1 compounds

ABSTRACT

The present invention provides 2-decarboxy-2-aminomethyl-6-hydroxy-PGE 1  compounds which are useful pharmacological agents. These analogs are useful as prostacyclin-like drugs.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation-in-part of Ser. No. 812,794, filed July 5, 1977, now issued as U.S. Pat. No. 4,131,738.

The present invention relates to 2-decarboxy-2-aminomethyl-6-hydroxy-PGE₁ compounds, the preparation and use of which are described in U.S. Ser. No. 812,794, filed July 5, 1977, now issued as U.S. Pat. No. 4,131,738 on Dec. 26, 1978.

The essential material constituting a disclosure of the instant invention is incorporated by reference here from U.S. Pat. No. 4,131,738. 

I claim:
 1. A prostacyclin analog of the formula ##STR1## wherein L₂ and L₃ are hydrogen or alkyl of one to 4 carbon atoms, inclusive, being the same or different;Wherein Z₁ is(1) --(CH₂)_(g) --CH₂ --CH₂ --, (2) --(ch₂)_(g) --CH₂ --CF₂ --, or (3) trans-(CH₂)_(g) --CH═CH--, wherein g is the integer one, 2, or 3; Wherein Y₁ is(1) trans--CH═CH--, (2) cis--CH═CH--, (3) --ch₂ ch₂ --, (4) trans--CH═C(Hal)--, or (5) --C.tbd.C--, wherein Hal is chloro or bromo; Wherein M₁ is ##STR2## wherein R₅ is hydrogen or alkyl with one to 4 carbon atoms, inclusive; Wherein L₁ is ##STR3## or a mixture of ##STR4## wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is fluoro only when the other is hydrogen or fluoro; and Wherein m is the integer one to 5, inclusive.
 2. A prostacyclin analog according to claim 1, wherein OH is beta.
 3. 2-Decarboxy-2-aminomethyl-6β-hydroxy-PGE₁, a prostacyclin analog according to claim
 2. 4. A prostacyclin analog according to claim 1, wherein OH is alpha.
 5. 2-Decarboxy-2-aminomethyl-6α-hydroxy-PGE₁, a prostacyclin analog according to claim
 4. 6. 2-Decarboxy-2-aminomethyl-6α-hydroxy-15-methyl-PGE₁, a prostacyclin analog according to claim
 4. 7. 2-Decarboxy-2-aminomethyl-6α-hydroxy-16,16-dimethyl-PGE₁, a prostacyclin analog according to claim
 4. 8. 2-Decarboxy-2-aminomethyl-6α-hydroxy-16,16-difluoro-PGE₁, a prostacyclin analog according to claim
 4. 9. A prostacyclin analog according to claim 1, wherein OH is a mixture of α--OH and β--OH.
 10. A prostacyclin analog according to claim 9, wherein Y₁ is cis--CH═CH--.
 11. 2-Decarboxy-2-aminomethyl-6-hydroxy-cis-13-PGE₁, a prostacyclin analog according to claim
 10. 12. A prostacyclin analog according to claim 9, wherein Y₁ is --C.tbd.C--.
 13. 2-Decarboxy-2-aminomethyl-6-hydroxy-13,14-didehydro-PGE₁, a prostacyclin analog according to claim
 12. 14. A prostacyclin analog according to claim 9, wherein Y₁ is trans--CH═C(Hal)--.
 15. 2-Decarboxy-2-aminomethyl-6-hydroxy-14-chloro-PGE₁, a prostacyclin analog according to claim
 14. 16. A prostacyclin analog according to claim 9, wherein Y₁ is --CH₂ CH₂ --.
 17. 2-Decarboxy-2-aminomethyl-6-hydroxy-13,14-dihydro-PGE₁, a prostacyclin analog according to claim
 16. 18. A prostacyclin analog according to claim 9, wherein Y₁ is trans--CH═CH--.
 19. A prostacyclin analog according to claim 18, wherein Z₁ is --(CH₂)_(g) --CH₂ --CF₂ --.
 20. 2-Decarboxy-2-aminomethyl-2,2-difluoro-6-hydroxy-15-methyl-PGE₁, a prostacyclin analog according to claim
 19. 21. A prostacyclin analog according to claim 18, wherein Z₁ is trans--(CH₂)_(g) --CH═CH--.
 22. 2-Decarboxy-2-aminomethyl-trans-2,3-didehydro-6-hydroxy-PGE₁, a prostacyclin analog according to claim
 21. 23. A prostacyclin analog according to claim 18, wherein Z₁ is --(CH₂)_(g) --CH₂ --CH₂ --.
 24. A prostacyclin analog according to claim 23, wherein g is one.
 25. A prostacyclin analog according to claim 24, wherein m is
 3. 26. A prostacyclin analog according to claim 25, wherein R₅ is methyl.
 27. 2-Decarboxy-2-aminomethyl-6-hydroxy-15-methyl-PGE₁, a prostacyclin analog according to claim
 26. 28. A prostacyclin analog according to claim 25, wherein R₅ is hydrogen.
 29. A prostacyclin analog according to claim 28, wherein at least one of R₃ and R₄ is fluoro.
 30. 2-Decarboxy-2-aminomethyl-6-hydroxy-16,16-difluoro-PGE₁, a prostacyclin analog according to claim
 29. 31. A prostacyclin analog according to claim 28, wherein at least one of R₃ and R₄ is methyl.
 32. 2-Decarboxy-2-aminomethyl-6-hydroxy-16,16-dimethyl-PGE₁, a prostacyclin analog according to claim
 31. 33. A prostacyclin analog according to claim 28, wherein R₃ and R₄ are both hydrogen.
 34. 2-Decarboxy-2-aminomethyl-6-hydroxy-PGE₁, a prostaglandin analog according to claim
 33. 